This Program Project will continue to investigate Photodynamic Therapy (PDT). The five projects will cover research topics ranging from cellular resistance to PDT to clinical trials for the treatment of brain tumors. The projects are supported by two core activities which are integral to their successful conduct. The synergy of the Program will continue to depend upon the effective interactions between both the scientific projects and the investigators. Project 1 proposes to investigate, in vivo, possible methods to improve the effectiveness of PDT by increasing availability of oxygen in the tumor at the time of treatment. Project 2 proposes clinical trials of PDT for the treatment of malignant brain tumors. Two trials involving Photofrin, one for de novo and one for recurrent lesions, are planned. Project 3 will continue to investigate cellular resistance to PDT. Knowledge regarding the mechanisms by which such resistance develops is critical to the understanding of PDT at the cellular level. Project 4 will continue to investigate PDT dosimetry. The studies proposed in this project will have a direct impact on the clinical application of PDT. Project 5 will continue its in vivo studies examining PDT effects in brain tumor and normal brain. One area of focus will be to investigate alternate methods of drug delivery. Core will provide overall technical support for the program. Calibration of devices and interproject quality assurance will be provided by this core.